趋化因子CXCL11激活NF-κB信号通路促进胰腺癌的侵袭转移及上皮间质转换

CXCL11 induces pancreatic cancer cell invasion and epithelial-mesenchymal transition in vitro through activation of NF-κB pathway

目的探讨NF-κB信号通路在趋化因子CXCL11诱导胰腺癌Panc-1细胞侵袭及上皮间质转换(EMT)中的作用。方法通过外源性CXCL11干预胰腺癌Panc-1细胞,以未干预组作为对照,Transwell小室侵袭实验检测各组Panc-1细胞的侵袭能力,Westernblot检测p65、P-p65、E-cadherin、N-cadherin和Vimentin的蛋白表达,免疫荧光检测p65的细胞内定位。使用NF-κB抑制剂BAY11-7082联合外源性CXCL11干预Panc-1细胞,再次通过Transwell小室侵袭实验检测各组Panc-1细胞的侵袭能力。结果外源性CXCL11可明显诱导Panc-1细胞侵袭(t=12.424,P<0.01),促进p65入核,并上调P-p65、N-cadherin和Vimentin,下调E-cadherin蛋白。抑制NF-κB通路后,外源性CXCL11失去了对胰腺癌细胞侵袭(P<0.01)和EMT的诱导作用。结论趋化因子CXCL11通过激活NF-κB信号通路,诱导胰腺癌细胞侵袭和EMT过程。

Objective To investigate the important role of NF-κB pathway in CXCL11-induced invasion and epithelial-mesenchymal transition (EMT) of pancreatic cancer cell line Panc-1. Methods Panc-1 cultured in vitro was harvested and divided into control group,CXCL11 group,and BAY 11-7082 group (NF-κB inhibitor). Transwell invasion assay was applied to analyze the invasive ability of tumor cells in different groups. The expressions of p65,P-p65,E-cadherin,N-cadherin,and Vimentin were determined by Western blot. The intracellular localization of p65 was detected by immunofluorescence staining. Results CXCL11 significantly induced the invasion of Panc-1 cells,promoted p65 nuclear translocation of Panc-1 cells,upregulated the expressions of P-p65,N-cadherin and Vimentin,and downregulated the expression of E-cadherin. Furthermore,the inhibition of NF-κB pathway obviously abrogated CXCL11-induced invasion of Panc-1 cells and enhanced the p65 nuclear translocation. Conclusion CXCL11 induces epithelial-mesenchymal transition and enhances invasion of pancreatic cancer cells through the activation of NF-κB pathway.